This project involves the use of monoclonal antibodies (MAbs) in both diagnostic and therapeutic clinical trials. To date, over 1,000 patients have been administered radiolabeled B72.3 in tumor-targeting studies carried out in numerous institutions, with similar findings of approximately 70-80% tumor targeting observed. The selective localization of 131-I MAb B72.3 IgG was demonstrated in biodistribution studies in colorectal cancer patients in which the percentage of injected dose of MAb per gram of each tumor was compared with that of the normal tissues, thus providing a relative radiolocalization index (RI) for each lesion. Of the tumor lesions, 70% had an RI of at least 3 (i.e., 3 times greater uptake per gram than normal tissues). We have also conducted studies to determine the feasibility of intraperitoneal administration of radiolabeled B72.3 for tumor localization (via both gamma scanning and direct analysis of biopsy specimens). A phase I therapy trial involving intraperitonel administration of l3lI-B72.3 IgG in patients with ovarian or colorectal carcinoma confined to the peritoneal cavity is in progress. The use of recombinant/chimeric MAbs has also begun and the use of second and third generation MAb-isotope conjugates are planned.